The objective of this study is to elucidate the cellular and molecular mechanisms of neoplastic development and to understand how environmental agents influence the progression of normal cells to malignancy. The specific aims of the research are: (1) determination of the differences between normal and tumorigenic cells: (2) identification of preneoplastic stages during neoplastic development; and (3) determination of whether the transitions of normal cells to preneoplastic cells, of preneoplastic to neoplastic cells, and of benign to malignant cells are mutagenic events or not. The studies involve model systems of oncogenesis which employ fibroblasts and epithelial cells in culture.